Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems, capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use. This long-awaited advance reflects recent development of chronically stable implantable biosensors, able to accurately measure biomarker levels in vivo...

The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...

Brigatinib (BGB) belongs to a class of drugs called ALK inhibitor. On April 28, 2017, BGB has been approved by U.S. FDA for use in metastatic ALK-positive NSCLC. A fast, specific, sensitive and validated LC-MS/MS method was developed for the quantification of BGB in human plasma matrix. This method was applied successfully to study metabolic stability of BGB. Reversed phase (C18 column) and isocratic binary mobile phase (55% 0.1% formic acid: 45% ACN) were used for chromatographic separation of BGB and ponatinib (IS)...

There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...

BACKGROUND: Substance use disorders (SUDs) are a leading cause of disability worldwide. While several pharmacological and behavioral treatments for SUDs are available, these may not be effective for all patients. Recent studies using non-invasive neuromodulation techniques including Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS) have shown promise for SUD treatment. OBJECTIVE: Multiple studies were evaluated investigating the therapeutic potential of non-invasive brain stimulation techniques in treatment of SUDs...

BACKGROUND: Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects. OBJECTIVES: To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase to September 2017...

BACKGROUND: Many patients experience complications following critical illness; these are now widely referred to as post-intensive care syndrome (PICS). An interprofessional intensive care unit (ICU) recovery center (ICU-RC), also known as a PICS clinic, is one potential approach to promoting patient and family recovery following critical illness. OBJECTIVES: To describe the role of an ICU-RC critical care pharmacist in identifying and treating medication-related problems among ICU survivors...

BACKGROUND: Ganciclovir-resistant cytomegalovirus (GR-CMV) is a serious complication of transplantation. Recurrence after primary infection is common. Little is known about CMV drug resistance and latency. OBJECTIVE: Review CMV genotype during episodes of recurrent CMV viremia after prior documentation of ganciclovir resistance to evaluate if resistance is redemonstrated. METHODS: All adult transplant recipients with history of GR-CMV viremia from January 1, 2011, to December 31, 2015, were screened; those with subsequent laboratory evidence of recurrent CMV viremia and genotyping were included...

OBJECTIVES: To review the immunogenicity, efficacy, and safety of the herpes zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of shingles. DATA SOURCES: A literature search through PubMed was conducted (June 2008 to October 2017) using the terms shingles vaccine and varicella zoster virus. References from retrieved articles and the prescribing information were also reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English...

BACKGROUND: Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited. AIM: To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis. METHODS: A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom...

We present the case of a 26-year-old man who was brought into our emergency department in cardiorespiratory arrest, having taken Kratom 24 h previously. Despite multi-organ support, he deteriorated and died from cardiorespiratory failure and hypoxic brain damage 12 h later. Lipid emulsion was given, with significant temporary improvement in the cardiorespiratory failure. Kratom is derived from Mitragyna speciosa, a tropical deciduous and evergreen tree in the coffee family, and is native to Southeast Asia, and its leaves are used as a legal high in some parts of the world...

Breast cancer is the most common cause of skin metastases in women. The probability of their occurrence ranges from about 5% in the entire population to as much as 30% in the late stages of the disease. Although rarely life-threatening, they have a major impact on the quality of life of patients with this diagnosis, being the cause of pain, effusion, ulceration, infection, and psychological discomfort. Available methods of treatment, both local and systemic, often fail to provide adequate control of the disease...

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...

Background: Herbal medicine (HM) regulation is less developed than that of allopathic medicines, with some countries lacking specific regulations. Objective: For the purpose of informing a registration system for HMs in Kuwait, which does not manufacture but imports all HMs, this study compared the similarities and differences between the current HM registration systems of five countries. Methods: The five countries were selected as major source countries of HM in Kuwait (United Kingdom (UK), Germany and United States of America (USA)) or because of geographical proximity or size and approach (United Arab Emirates (UAE) and Kingdom of Bahrain)...

Substance use disorders are comparable to chronic medical illnesses and have a chronic relapsing course. Despite being significant contributors to morbidity and mortality, limited treatment options exist. The current narrative review was aimed at providing an overview of yoga therapy in substance-use disorders and discuss the relevant methodological issues. Articles published in English language till May 2017 indexed with PubMed, PubMed central, and Google Scholar were searched using search terms "Yoga," "Substance use," "Drug dependence," "Nicotine," "Tobacco," "Alcohol," "Opioids," "Cannabis," "Cocaine," "Stimulants," "Sedative hypnotics," "Inhalants," and "Hallucinogens" for inclusion in the review...

Recent evidence has indicated that cannabis use before driving is associated with a modest but increased risk for traffic-related injuries. However, the question of whether recent cannabis use is associated with a greater risk for other types of injuries remains unanswered. Aiming to understand better how acute cannabis use might affect the risk for all causes of injury, we have summarized the limited data available in the literature on the risk of non-traffic injuries associated with recent cannabis use. Very few studies were able to provide estimate risks for all injuries or injuries other than those related to road traffic injuries, with the limited evidence available showing mixed findings...

Although it has long been demonstrated that cytosolic DNA is a potent immune stimulant, it is only in recent years that the molecular mechanisms of DNA-stimulated innate immune responses have emerged. Studies have established critical roles for the DNA sensor cyclic GMP-AMP synthase (cGAS) and the adapter protein MITA/STING in the innate immune response to cytosolic DNA or DNA viruses. Although the regulation of cGAS-MITA/STING-mediated signaling remains to be fully investigated, understanding the processes involved may help to explain the mechanisms of innate immune signaling events and perhaps autoinflammatory diseases and to provide potential therapeutic targets for drug intervention...

Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipruritic therapies are usually practiced in the treatment of pruritus including general preventive measures, topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin, corticosteroids, immunomodulators and; systemic therapies including administration of antihistamines, opioid antagonists/agonists, antiepileptic drugs/neuroleptics (e...